tbuckley/cabot-search huggingface dataset:
Abstract 13399: A Case of Propofol-Induced Takotsubo Cardiomyopathy
Authors: Deborah A Aina, Chad Nicholson, Delano Small
Journal: Circulation (2022)

Introduction: Takotsubo syndrome (TS) is a transient cardiomyopathy characterized by an apical ballooning appearance, mimicking a myocardial infarction. Stress-induced catecholamine excess is the best studied hypothesis. There have been few reported cases of TS following induction of anesthesia. This is the first case that describes propofol as an inciting factor in the development of TS. Case report: A 75-year old male with history of COPD, recurrent pneumothorax, pharyngeal cancer, and no prior cardiac history, presented with dyspnea. Chest x-ray revealed a right-sided pneumothorax. Plan was to proceed with thoracoscopy and talc pleurodesis. He underwent induction of general anesthesia with propofol. Following induction, he went into asystole, requiring a round of CPR prior to ROSC and transfer to the ICU. Troponin was elevated at 1.12. EKG revealed diffuse ST-segment elevation. ECHO showed EF 15-20%, with severe global hypokinesis, a hyperdynamic left ventricle at the base, concerning for TS (Figure 1). Repeat ECHO eight days later, revealed a recovered EF of 70-75%. The most likely diagnosis was TS. Discussion: This case identifies propofol as an inciting factor in the development of TS during the induction of general anesthesia. Propofol is a sedative-hypnotic, used in the induction and maintenance of general anesthesia. It works by decreasing the dissociation from GABA receptors, leading to an inhibitory effect on wakefulness. However, it also adversely acts at the cellular level as a calcium antagonist, reducing vascular tone, leading to hypotension and depression of myocardial contractility. We postulate that the inhibitory effects of propofol on the cardiovascular system, likely contributed to the development of TS in our patient. Conclusion: In conclusion, use of propofol during the induction process may be an important risk factor in the development of TS. This is an important consideration when choosing induction agents, in high risk patients.
Abstract 12958: The Dark Side of Normal Healing: Fibrous Encasement of a Subcutaneous ICD Coil
Authors: Kevin Liu, Ele Wu, Ekin Uzunoglu, Claude elayi, John Catanzaro
Journal: Circulation (2022)

Introduction: Implantable devices elicit fibrotic and inflammatory responses, which may result in reduced efficacy of the device. Prior literature has addressed thrombus formation and fibrous encapsulation of intravascular leads. This mechanism is at least in part different than subcutaneous fibrosis. However, there have been scarce reports of fibrosis related to subcutaneous leads. Case: A 74 year-old male with long standing ischemic cardiomyopathy and absence of pacing indication met indications for primary prevention S-ICD. After shared decision making, a device was implanted with defibrillation thresholds at 65 joules. He later presented with interventricular dyssynchrony (QRS 160 msec) and symptomatic heart block. Upgrade to a biventricular defibrillator was undertaken with removal of the S-ICD system. S-ICD coil manual traction failed to free the lead from the subcutaneous space of implantation. After extensive blunt dissection and removal of the coil, extensive coil ingrowth and fibrosis was noted (Figure 1). Conclusions: This case describes the occurrence and visually documents extravascular coil fibrosis and ingrowth into the SICD coil, similarly seen in intravascular ICD leads. The S-ICD coil is a necessary component of the shocking vector and extensive fibrosis may contribute to elevated shock impedance and failed defibrillation thresholds. In cases of elevated shock impedance, it is unknown whether failed defibrillation thresholds or elevated high voltage shock impedance is the result of the generator, coil, or both. Further research is warranted to ascertain whether failed defibrillation thresholds and increased shock impedance is due solely from the SICD generator pocket. Advances in coil technology and regenerative medicine may offer insights into mitigation of the inflammatory process.
Abstract 13505: COVID-19 and Cardiovascular Disease Patient Hearts Harbor Sympathetic Remodeling and Altered Angiotensin Converting Enzyme 2 Localization
Authors: Creighton L Kellum, Tasha K Nelson, Paul V Benson, Brant M Wagener, Donald B Hoover
Journal: Circulation (2022)

Cardiac complications of COVID-19 have been well described and are associated with significant morbidity and mortality. Concomitantly, various pre-existing cardiovascular diseases (CVDs) are established risk factors for developing severe COVID-19 illness and death. The mechanisms of cardiac injury after COVID-19 remain incompletely understood. Further, whether and how SARS-CoV-2 directly infects the heart is unclear. In this study, we investigated cardiac sympathetic innervation and the cellular localization of angiotensin converting enzyme 2 (ACE2) to test the hypothesis that pre-existing or acute changes in these parameters could contribute to cardiac complications of COVID-19. We performed immunohistochemical (IHC) analysis on sections of left ventricular (LV) wall from twenty autopsied human hearts consisting of a control group, a CVD group, and COVID-19 ARDS and COVID-19 non-ARDS groups. Using tyrosine hydroxylase as a noradrenergic marker, we observed substantial sympathetic nerve loss in CVD LVs compared to the control group, which is consistent with previous work suggesting loss of sympathetic activity in severe heart failure. Additionally, we observed mild and heterogeneous nerve loss in both COVID-19 groups. Using an ACE2 antibody, we observed robust transmural staining localized to pericytes in the control group. The CVD hearts displayed significant loss of ACE2 in pericytes and increased ACE2 in cardiomyocytes. Both COVID-19 groups displayed a modest increase in cardiomyocyte ACE2 compared to controls, and pericyte ACE2 staining was generally maintained. We also performed IHC for PDGF receptor β, an established marker for pericytes, and confirmed ACE2 localization to pericytes. The observed sympathetic nerve remodeling could play a key role in arrhythmogenesis in acute or post-acute COVID-19 patients. Further, if SARS-CoV-2 does infect the heart, then our data demonstrate the primary target would be through microvasculature associated pericytes, not cardiomyocytes. Finally, the upregulation of cardiomyocyte ACE2 in both CVD and COVID-19 groups could play a contributing role in COVID-19 associated cardiac injury or a compensatory role in cardiac pathogenesis by attenuating the local effects of angiotensin II.
Abstract 13589: Strong African Immigrant Social Network Influences Self-Care of African Immigrants With Chronic Illness
Authors: Onome H Osokpo, Christin Iroegbu, Lisa M Lewis, Liming Huang, Karen Hirschman, Mary D Naylor, Barbara J Riegel
Journal: Circulation (2022)

Background: Self-care is a fundamental component of chronic illness management. Although, there is increasing recognition that social networks can substantially impact the self-care of individuals with chronic illness, little is known about how social networks are associated with self-care among African immigrants living with hypertension, diabetes, or other chronic illness in the US. Methods: In this descriptive, cross-sectional study, we enrolled a convenience sample (n=128) of self-identified sub-Saharan African immigrants in the Northeastern U.S. age ≥ 35 years, with symptomatic chronic illness, who spoke and understood English. Self-care was measured with the Self Care of Chronic Illness Inventory measuring self-care maintenance, monitoring, and management (scores standardized 0-100, ≥70 adequate self-care). Social network was measured using four items that assess social network either with Americans or other African immigrants (e.g., “I spend my free time with African people”) using a 5-point response scale (1-Never to 5-Always); higher score=better social network. Multivariable linear regression was used to assess associations between social network and self-care adjusting for age, gender, marital status, education, employment status, and duration of US residency. Results: The sample on average was 56 years old (±11 years), male (68%), married (70%), college educated (82%), employed (66%), lived with family or others (89%), and had a long duration of residency (16±11 years). Most participants had hypertension (48%) and/or diabetes (20%). Self-care scores were adequate ( x 78.7, 79.3, 73.9 for self-care maintenance, monitoring and management). Social network as a composite score was positively associated with self-care maintenance (p=0.06). Social network with other African immigrants had a positive association with self-care maintenance (p=0.03) while social network with American people was not associated with self-care. Conclusions: In this sample of African immigrants, self-care was adequate. Having a strong social network with other African immigrants promoted self-care maintenance. Social networks of African immigrants can be used and harnessed in developing culturally concordant self-care interventions.
Abstract 13457: Ability of CHARGE-AF and CHA <sub>2</sub> DS <sub>2</sub> -VASc Scores to Predict Prevalent Atrial Fibrillation in a High-Risk Population
Authors: Hassan Chami, Linzi Li, Arshed A Quyyumi, Alvaro Alonso
Journal: Circulation (2022)

Introduction: The CHARGE-AF score estimates 5-year risk of developing atrial fibrillation (AF) using information on age, race, weight, height, systolic and diastolic blood pressure, diabetes, smoking, use of antihypertensive medication, and prevalence of heart failure and myocardial infarction. Similarly, the CHA 2 DS 2 -VASc score for estimation of stroke risk in AF has been proposed as a useful tool for incident AF prediction. It is unclear whether these scores can predict AF in a high-risk population. We evaluated whether the CHARGE-AF and CHA 2 DS 2 -VASc scores predict the prevalence of AF in the Emory Cardiovascular Biobank cohort (EmCAB) that recruited patients undergoing cardiac catheterization with suspected or confirmed coronary artery disease. Methods: In 6951 EmCAB participants, logistic regression was used to determine the association between baseline characteristics, CHARGE-AF and CHA 2 DS 2 -VASc scores and the presence of prevalent AF. To assess the discrimination of the CHARGE-AF and CHA 2 DS 2 -VASc models, we estimated the C-statistic. Internal calibration was determined with the Hosmer-Lemeshow test. Results: Mean age of patients was 62 (SD=13), 64% male, 76% White. Median 5-year risk of AF using the CHARGE-AF score was significantly higher in those with compared to those without prevalent AF (11% vs. 4%, p=&lt;0.001). However, the median CHA 2 DS 2 -VASc scores were similar in both groups (3.0). The C-statistic for predicting prevalent AF was better with the CHARGE-AF compared to the CHA 2 DS 2 -VASc score (0.662 vs. 0.606). The strongest risk predictor of prevalent AF was heart failure (OR 2.52, 95%CI 2.13-2.98). Conclusion: In a high risk cohort of patients with CAD, the CHARGE-AF score had a moderate discrimination ability to predict AF and showed better performance than the CHA 2 DS 2 -VASc score. Whether the CHARGE-AF score is useful in predicting incident AF in high risk patients needs to be further investigated.
Abstract 12960: Effect of Iron Therapy on Exercise Capacity and Quality of Life in Patients With Systolic Heart Failure: A Systematic Review and Meta-Analysis
Authors: Angkawipa Trongtorsak, Pabitra Adhikari, Sittinun Thangjui, Jakrin Kewcharoen, Solab Chitrakar, Natnicha Leelaviwat, Juthipong Benjanuwattra, Pattara Rattanawong, Muhammad S Akbar
Journal: Circulation (2022)

Background: Iron deficiency in patients with systolic heart failure (HF) was found to be associated with poorer exercise capacity and quality of life. We conducted this systematic review and meta-analysis to assess whether iron supplementation in patients with systolic HF can improve exercise capacity and quality of life. Methods: We searched MEDLINE, and Embase databases from inception to May 2022 to identify the studies that reported the impact of iron therapy including oral and intravenous (IV) iron forms in systolic HF patients with iron deficiency. Outcomes of interest included 1) six minute walk test (6MWT) and 2) Quality of life (QoL) assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ). Data from each study were combined using the random-effects model to calculate weight mean difference (WMD) and 95% confidence interval (CI) Results: Five studies (4 randomized controlled trials and 1 nonrandomized open-label study) with a total of 1,075 patients (610 in the intervention group and 465 in the control group) were included. In the intervention group, 474 patients received IV iron and 136 patients received oral iron therapy. Iron therapy was associated with significant improvement of 6MWT (WMD =22.81, 95% CI 0.47-45.14, p &lt; 0.001) and KCCQ (WMD =4.68, 95%CI 0.43-8.93, p&lt; 0.001). Interestingly, subgroup analysis showed that the main results were driven by IV iron therapy in both 6MWT (WMD =34.68, 95%CI 25.13-44.24, p&lt; 0.001) and KCCQ (WMD =6.78, 95%CI 3.81-9.75, p&lt; 0.001) as there was no significant improvement after oral iron therapy in 6MWT (WMD =0.15, 95% CI -23.86-24.16, p =0.99) and KCCQ (WMD =2.71, 95% CI-1.35-6.78, p =0.19). As shown in Figure 1. Conclusions: Intravenous iron therapy, but not oral iron therapy is associated with improved exercise capacity and QoL in patients with systolic HF.
Abstract 12946: L-Arginine Attenuates Myofibroblast Phenoconversion and Fibrosis in the Human Heart
Authors: Fahimeh Varzideh, Stanislovas Jankauskas, Xujun Wang, Pasquale Mone, Angela Lombardi, Gaetano Santulli
Journal: Circulation (2022)

Introduction. L-Arginine (L-Arg) is a semi-essential amino acid involved in a number of biological processes. L-Arg has been recently shown to have beneficial effects on functional capacity in heart failure. However, the molecular mechanism underlying these actions are mostly unknown and a potential direct effect of L-Arg on cardiac fibroblasts has never been investigated hitherto. Transforming growth factor (TGF)-β is one of the main profibrotic cytokines, known to activate fibroblasts into myofibroblasts stimulating the production of extracellular matrix (ECM). In fibrosis condition, excessive ECM alters myocardial structure, eventually impairing cardiac function. Hypothesis. We hypothesized that L-Arg could mitigate TGF-β-dependent phenoconversion of human cardiac fibroblasts (HCFs). Methods. We isolated primary cardiac fibroblasts from human hearts (protocol approved by the Institutional Review Board for protection of human subjects) and tested a model of fibrosis obtained by treatment with TGF-β. Isolated HCFs were characterized by immunostaining. Early passage HCFs were treated with TGF-β or TGF-β + L-Arg at different doses and time points. The mitochondrial generation of reactive oxygen species (ROS) was assessed by MitoSox at the confocal microscopy. Results. TGF-β induced a significant upregulation of established markers of myofibroblast activation and fibrosis (including Fibronectin, Col1A1, Col1A2, and Periostin ), which was significantly attenuated by L-Arg, as confirmed by RT-qPCR, immunostaining, and immunoblot. Moreover, we observed that TGF-β treatment significantly increased the mitochondrial generation of ROS, which was again prevented by co-treatment with L-Arg. In addition, L-Arg significantly reduced SMAD-2 protein expression. Conclusions. Our findings demonstrate, for the first time to our knowledge, the anti-fibrotic role of L-Arg in HCFs, mediated via a TGF-β/SMAD-2 signaling pathway.
Abstract 12785: Psat1 Promotes Serine Synthesis Pathway and Cardiac Regeneration After Myocardial Infarction
Authors: Ajit Magadum, Vandana Mallaredy, Rajika Roy, Chunlin Wang, Grace Grace, Zhongjian Cheng, May Truongcao, Darukeshwara Joladarashi, Charan Thej Gurrala, Vagner O Rigaud, Anna Maria Lucchese, Cindy Benedict, Mohsin Khan, Celio X Santos, Ajay M Shah, Walter J Koch, Raj Kishore
Journal: Circulation (2022)

Introduction: Permanent loss of cardiomyocytes (CM) after myocardial infarction (MI) and limited cardiac regenerative capacity lead to heart failure. The iPSC-derived extracellular vesicles (EV) have been shown to improve cardiac function and protection. However, the iPSC-EVs-mediated cardiac function improvement mechanism remains unclear and largely pertains to microRNAs and other RNAs, with a little elucidation of the role of iPSC-EV proteins. Hypothesis: The myocardial delivery of hiPSC-EV-specific protein PSAT1 (phosphoserine aminotransferase 1) induced cardiac regeneration and improved cardiac function post-MI by activating CM proliferation and anti-oxidative stress molecular pathways. Methods and Results: We show that hiPSC-EVs treatment augmented cardiac functions and induced a significant CM cell cycle in mice post-MI. Proteomic analysis identified PSAT1 as a protein expressed exclusively in hiPSC-EVs. The role of PSAT1 in CM proliferation and cardiac regeneration is not studied. The PSAT1 expression was significantly downregulated with heart development. Cardiac delivery of PSAT1 modified mRNA (modRNA) induced a significant CM proliferation post-MI. This increase in the CMs proliferation by the PSAT1 modRNA was associated with reduced scar size, improved cardiac function and CM survival, reduced oxidative stress, and CM apoptosis post-MI. Furthermore, the PSAT1 modRNA inhibited the CM apoptosis by reducing oxidative stress and DNA damage response post-MI. Moreover, we show that the YAP, a master regulator of CM proliferation and cardiac regeneration, binds to the promoter of PSAT1 and induces its expression. Finally, PSAT1 modRNA induced the serine biosynthesis pathway in CMs, resulting in increased nucleotide synthesis and reduced oxidative stress, thereby supporting CM proliferation. Conclusion: Our studies uncover a novel role of hiPSC-EV specific protein PSAT1, and serine synthesis pathway activation leads to post-MI CM proliferation, inhibition of oxidative stress, and improved cardiac function. Furthermore, this work emphasizes the therapeutic prospect of using PSAT1 modRNA as a gene delivery approach for ischemic heart diseases.
Abstract 13086: Mid-Term Feasibility of Left Bundle Branch Area Pacing With Standard Stylet-Driven Pacing Leads and Predictors of Success: A Multicenter Center Experience
Authors: Yu Gain, Tae-Hoon Kim, Hee Tae Yu, BOYOUNG JOUNG, Hui-Nam Pak, Moon Hyoung LEE
Journal: Circulation (2022)

Introduction: Conventional right ventricular apical pacing can cause electrical-mechanical dyssynchrony. For this reason, physiological pacing was considered and became the background for the development of his bundle pacing (HBP). Recently, left bundle branch area pacing (LBBAP), which overcomes the shortcomings of HBP, has been implemented. Hypothesis: Initially, LBBAP was achieved through a lumen-less lead, and it has been reported that LBBAP using a standard stylet-driven lead (SDL) is also available. The purpose of this study is to establish the feasibility and mid-term outcome of LBBAP using SDL, and to investigate the predictors of success. Methods: This study enrolled a total of 119 patients who underwent LBBAP from December 2020 to February 2022. LBBAP was performed with a 5.6Fr stylet-driven pacing lead with an extendable helix (Solia S60, Biotronik, SE &amp; Co, KG). We analyzed the initial outcomes of the procedure, including the success rate and complications, and identified predictive factors that affect them. lead parameters were assessed in follow up. Results: Total success rate of lead implantation of LBBAP with conventional stylet-driven lead was 95.8% for entire period and showed increase in success rate as the number of procedures increased. In the multivariate analysis, The larger the RA size, the greater the number of trials (Estimates = 1.770 [1.10 - 2.44], p = &lt;0.001) and the smaller the RV size, the greater the number of trials (Estimates = -0.923 [-1.64 - -0.21], p = 0.012). The mean thresholds at implant, 2 months, 6 months were 0.90 ± 0.80 V at 0.5 ms, 0.80 ± 0.16 V at 0.5 ms, and 0.87 ± 0.28 V at 0.5 ms respectively in total period. Conclusions: LBBAP with conventional stylet-driven lead is a feasible and safe pacing modality. It has a high success rate and fewer complications, satisfied and stable lead parameters in intermediate-term observations.
Abstract 12894: Murine Arterial Wall Strain Estimation With Ultrasound-Based Lagrangian Carotid Strain Imaging and Validation Against Histological Findings
Authors: Rashid Al Mukaddim, Yuming liu, Melissa Graham, Jens Eickhoff, Ashley M Weichmann, Matthew C Tattersall, James H Stein, Tomy Varghese, Kevin Eliceiri, Carol Mitchell
Journal: Circulation (2022)

Introduction: Early identification of arterial injury by non-invasive imaging can facilitate research into mechanisms of arterial injury and has the potential to improve patient management. We tested the hypothesis that Lagrangian carotid strain imaging (LCSI) combined with adaptive Bayesian regularization could detect early arterial injury and monitor atherogenesis in a murine model by associating findings with histological examinations. Methods: Radio-frequency (RF) data were collected from the right and left common carotid arteries (CCA) of 10 (5 male and 5 female) ApoE tm1Unc/J mice at 6, 16 and 24 weeks using a high frequency ultrasound system. Cumulative axial, lateral and shear strain images were estimated using LCSI and 3 strain indices: maximum accumulated strain index (MASI), peak mean strain of full ROI index (PMSRI) and strain at peak axial displacement index (SPADI). Mice were euthanized (n=2 at 6 and 16 weeks, n=6 at 24 weeks) for histological examination. Results: We observed sex-specific differences in the temporal variation of strain indices. For male mice, axial PMSRI and SPADI changed significantly from 6 to 24 weeks (mean axial SPADI at 6 = 14.10±6.30 % and 24 weeks = 0.24±6.22%; p=0.0004). For female mice, lateral MASI was significantly higher at 24 than 6 weeks (mean lateral MASI at 6 = 10.26±3.13 % and 24 weeks = 16.42±7.15% p=0.048). Both sexes had strong associations with histological findings. For males, axial PMSRI and SPADI showed significant correlation with the number of elastin fibers (axial PMSRI: r s =0.83, p=0.01; axial SPADI: r s =0.76, p=0.02). For females, lateral and shear MASI had significant correlations with plaque scores (lateral MASI: r s =0.66, p=0.04; shear MASI: r s 0.77, p =0.009). Conclusions: LCSI can quantify carotid arterial wall strain in a murine model non-invasively. Changes in strain were associated with changes in arterial wall microstructure after plaque formation.